The Genetics of Aminoglycoside-Related Deafness

Abstract

Preterm infants are at high risk for both early-onset and late-onset, hospital-acquired bloodstream infections. Aminoglycoside antibiotics are commonly used in the empiric treatment of suspected infection among these infants. A number of mutations in mitochondrial deoxyribonucleic acid (mtDNA) are known to increase the risk of developing irreversible hearing loss after exposure to aminoglycoside antibiotics. These mutations modify the mitochondrial ribosome, increasing the binding affinity of aminoglycosides and resulting in inhibition of mitochondrial protein synthesis. The mitochondrial m.1555A>G mutation in the gene encoding the mitochondrial 12S ribosomal ribonucleic acid (rRNA) subunit is the most common mutation mediating aminoglycoside ototoxicity. The opportunity for effective prevention may be limited by the fact that an aminoglycoside, such as gentamicin, is frequently used in the first few days after birth to prevent possible early-onset sepsis. Screening at-risk mothers might overcome this problem, if there is clinical evidence that it can be performed in a timely manner to be clinically useful.